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12. hallmark of aging: altered autophagy

12 Hallmarks Of Aging Altered Autophagy

Altered (macro-) autophagy or, more precisely, altered cellular waste disposal is the twelfth and final hallmark of ageing. Science understands this to mean that our cells are no longer able to get rid of cellular waste. This can affect large molecule complexes or entire cell organelles - hence the prefix "macro" - but also the smallest deposits, such as those found in Alzheimer's dementia. For the sake of simplicity, we will only refer to autophagy in the rest of the article.

So why does cellular waste disposal play such an important role? To answer this in more detail, we will take you on a short journey through the body and introduce you to the various components of your waste disposal system. Don't be intimidated by complicated names like autophagic-lysosomal system or chaperones, we'll explain everything step by step. We'll also take a look at the research and explain why sleep and the supplementation of spermidine can be a booster for a weakening recycling system.

What is autophagy?

Autophagy describes the cell's own recycling process. It is completely normal for proteins or other cell components to lose their function or no longer be needed at some point. After all, our requirements change over time. Our cellular power plants - the mitochondria - do not last an entire human lifetime. The task of autophagy is to ensure that these remnants are broken down correctly and the components are then reused.

We have already identified the incorrect degradation of proteins, for example - the loss of proteostasis - as a hallmark of ageing. Here, incorrectly folded proteins can no longer be unfolded. This harbors the risk of clumping. However, as the disposal of proteins is only a small part of cellular waste disposal, the hallmarks of ageing have been expanded. Since the last update, altered autophagy has become a Hallmark in its own right. Here we show you exactly what happens to it as we age.

Spermidine Autophagy

From scissors to acid traps - how is the waste in our cells disposed of?

Before we look at what no longer works properly in old age, we should first take a closer look at our recycling system. It is quite elegantly designed and does its job day after day without us noticing.

Roughly speaking, there are two major systems in the waste disposal of cells. The first has the cumbersome name ubiquitin-proteasome system (UPS) and has two main tasks. On the one hand, the labeling (ubiquitination) of misfolded proteins and, on the other hand, the proteasomes ensure that these misfolded proteins are broken down into their individual amino acids.

You can imagine the proteasomes as a kind of filter with highly specialized scissors inside. All proteins that enter the proteasomes are neatly separated and are then available to the cell as new building blocks.

The second large system bears the no less complicated name autophagic-lysosomal system. This is more complex in structure than the UPS, as it not only breaks down individual proteins, but in cases of doubt, entire cell organelles are broken down into their building blocks and these are then returned to the cell metabolism.

The 4th Hallmark of Aging is largely based on a malfunction of the ubiquitin-proteasome system. This is now about autophagy.

Autophagy Cellular waste disposal
Just as mountains of garbage often accumulate in nature, this also happens to us humans in old age.

The autophagic-lysosomal system

In our cells, it is not only faulty proteins that are a problem, but also cell organelles that no longer function. We have already written extensive articles about the role of ATP and the mitochondria, but these reveal little about what happens when old mitochondria have to be broken down. This happens through macroautophagy.

Again, this is shown in simplified form: A sheath forms around the old mitochondrion, which in its entirety is called an autophagosome. Now we have a protected environment. This is necessary so that the degradation inside the cell does not immediately destroy the entire cell.

In the next step, the autophagosome combines with the lysosome. This is a kind of small stomach - it contains lots of digestive enzymes that we need to break down complex molecules. Everything is now broken down within this protected environment and, as always in biology, there is now also a new name. The autolysosome is the combination of the autphagosome and the lysosome.

After digestion, everything that can be reused is returned to the cell and the waste products are removed with the lymphatic fluid.

Lipofuscin - when you can literally see your age

In old age, our highly specialized recycling system can no longer keep up. If we stay with the lysosomes, this can be seen impressively. In addition to their task as "waste shredders", these cell organs can also absorb large proteins that no longer have a function in the cell but are too large to be transported away with the lymph or via the bloodstream. This "hazardous waste" is stored in the cell in small capsules known as "granules".

If you look at old nerve or muscle cells under a microscope, you can see many of these dark spots. To a large extent, this is lipofuscin. It consists mainly of damaged mitochondria that can no longer be broken down properly. The cellular waste virtually "clogs" the cell and thus restricts its function. This is probably one of the reasons why mitochondrial dysfunction occurs in old age.

Lipofuscin Age spots Autophagy
Age spots are not only seen in nerve cells under the microscope, but also in ageing skin.

Alzheimer's - one of the most prominent examples of incorrect waste disposal

Alzheimer's dementia is another disease that is associated with faulty waste disposal. Here, so-called amyloid plaques are deposited. These complexes accumulate in the nerve cells due to faulty degradation and "litter" them.

In addition, the tau protein - a protein that is important for cell stability - is altered in Alzheimer's patients. The result is an unstable cell and the death of neurons.

Alzheimer's has become a widespread disease over the decades. The risk factors are partly genetic and partly lifestyle-related. Incorrect waste disposal definitely plays an important role in the development of this as yet incurable disease.

Sleep - a long underestimated remedy

There are many ways to help our body with autophagy. One very promising one is to get enough sleep. While we slumber peacefully, our brain is being tidied up. The so-called glymphatic system ensures that the waste products of the day are removed.

For a long time, sleep was somewhat neglected in medicine, but we now know that sleep is extremely important for our health. If we don't get enough sleep for months or years, cellular waste cannot be removed properly and the risk of Alzheimer's increases.